A physiologically active substance, called "pulmonary surfactant", composed mainly of phospholipids exists in the animal lungs. The pulmonary surfactant is mainly biosynthesized in and secreted from type II epithelial cells of the alveoli, and is known to be present as an internal lining of the wall of the whole respiratory tract including the alveolar region. It is known that pulmonary surfactant reduces the surface tension of the alveoli and prevents collapse of the alveoli. This action is of great physiological importance in that it helps to maintain respiratory function (L. G. Dobbs: Annual Rev. of Med., 40, 431-446, 1989). Infant respiratory distress syndrome which may lead to acute respiratory failure is caused by a deficiency of pulmonary surfactant. It is well documented that in adult respiratory distress syndrome decrease or dysfunction of pulmonary surfactant is also found. Moreover, Hallman et al. reported that in chronic diseases associated with respiratory failure, too, abnormality of pulmonary surfactant may occur (Journal of Clinical Investigation 70: 673-683, 1982).
Pulmonary surfactant plays an important role as a defense mechanism in the entire respiratory tract, as well as the anticollapse action. Thus, it is well documented that it prevents pulmonary edema and has preventive effects on bacterial or viral infection or on atmospheric pollutants and antigens which induce inflammation of the respiratory tract or asthmatic attacks. Moreover, pulmonary surfactant is known to play an important role in lubricating the respiratory lumen and expelling any foreign matter from the respiratory tract by activating mucociliary transport. As described above, pulmonary surfactant discharges various physiological functions in the respiratory system and, therefore, qualitative and quantitative changes of pulmonary surfactant seem to be related to the onset or aggravation of many respiratory diseases. Accordingly, the promotion of secretion of pulmonary surfactant may make it possible to treat or prevent various respiratory diseases, for example acute respiratory failure such as infant or adult respiratory distress syndrome, acute or chronic bronchitis, infectious disease, asthma and chronic respiratory failure.
Furthermore, it is thought that administration of pulmonary surfactant to a pregnant woman who may deliver an immature infant can prevent the onset of infant respiratory distress syndrome. Attempts have heretofore been made to utilize the naturally-occurring or genetically engineered pulmonary surfactant as such or a composition containing such pulmonary surfactant as the pulmonary surfactant (JP-B-1-13690, JP-A(PCT)-63-501792 and JP-A-2-53798, corresponding to U.S. Pat. No. 4,828,844, WO-8702037 and EP-A-0348967, respectively, the term "JP-A" as used herein means an "unexamined published Japanese patent application" and "JP-B" as used herein means an "examined Japanese patent publication") but as far as the activity to promote secretion of the endogenous pulmonary surfactant is concerned, ambroxol hydrochloride which is commercially available as an expectorant (Merck Index 11, pp. 62-63, 392 Ambroxol) is the only substance known to have such activity (Post et al.: Lung 161, 349-359, 1983).
Meanwhile, as a compound having the structure of 1,3- dihydro-2H-benzimidazol-2-one, a compound having a 3-dimethylaminopropyl group at the 1-position and no substituent on the benzene ring is described in Spectroscopy Letters, 5(9), 293 (1972) but the literature contains no description of its pharmacological activity. Aside from the above compound, the compound having a 2-diethylaminoethyl group at the 1-position and no substituent on the benzene ring and the compound having a 3-dimethylaminopropyl group at the 1-position and a chloro substituent at the 6-position are described in J. Chem. Soc., 314 (1960). In regard to pharmacological activity, however, it is only mentioned that 1-alkyl-2-oxobenzimidazoline compounds exhibit spinal reflex depressant activity, which is quite alien to the pharmacological activity according to the present invention, without giving specific pharmacological data.
A compound having a 2-piperidinoethyl group at the 1-position and no substituent on the benzene ring is also described in JP-A-62-252721. However, this compound is merely claimed to be useful as a peptic antiulcer agent. Thus, none of the literature mentioned above disclose any benzimidazolinone derivative having pulmonary surfactant secretion stimulatory activity as proposed by the present invention.